DESCRIPTION, OVERALL (provided by applicant): The Center for the Study of Inflammatory Bowel Disease (CSIBD) is a multidisciplinary program to define fundamental mechanisms underlying Crohn's disease and Ulcerative colitis. This Center encompasses seventy-two investigators at the Massachusetts General Hospital (MGH) and allied institutions pursuing research in a broad spectrum of basic science relevant to IBD. Since is formation fourteen years ago, the CSIBD has served as a vehicle to achieve advances in our understanding of these diseases through the study of relevant basic biological processes and the directed study of the diseases themselves. The research program of this Center is organized around the central hypothesis that IBD results from activation by luminal bacteria or their products of an upregulated chronic immune response due to genetically determined alterations of epithelial cell or immune function including a lack of appropriate downregulatory functions. Major advances made possible by the CSIBD in the years since its inception include the development and characterization of new genetic mouse models of IBD, delineation of mechanisms of lymphocyte activation and leukocyte recruitment to sites of inflammation, characterization of mechanisms of innate immune response, identification of key peptides involved in sustaining mucosal integrity, characterization of the mechanisms of mucosal healing following injury, improved understanding of the regulation of epithelial function and mucosal immune responses and the delineation of the mechanisms of mucosal:microbial interaction. Over the next five years, the CSIBD will promote further progress in the study of basic aspects of mucosal biology with translation for the study and treatment of IBD. A major focus of CSIBD research in the next five years will be the coordinated multi-disciplinary study of mechanisms leading to chronic intestinal inflammation and delineation of interactions between environmental factors and different genetic loci. The center will also actively promote clinical and translational research efforts to apply insights gained in studying various disease mechanisms. The overall goal of advancing our knowledge of IBD will continue to be carried out through five Biomedical Cores. These include Molecular Biology, Morphology and Immunology Cores to provide access to advanced technologies. The Genetic Animal Models and Clinical/Tissue Cores provide access to relevant animal models and patients for study. In addition to advancing the understanding of IBD per se, the goals of this Center will continue to include the recruitment of established investigators to the study of IBD, enhancing collaboration among Center investigators and encouraging the development of junior investigators committed to pursuing IBD research. These goals are fostered by Pilot/Feasibility Study awards which support new research initiatives as well as an Enrichment Program of seminars, workshops and symposia.